idetrexed + olaparib

idetrexed + olaparib is a combination therapy being evaluated in the Phase I/Ib IDOL clinical trial for the treatment of high-grade serous ovarian cancer, specifically targeting tumors that overexpress the alpha-folate receptor (FRα). Idetrexed (formerly ONX-0801 or BTG945) is a small-molecule thymidylate synthase inhibitor designed to selectively enter cancer cells via FRα, which is highly expressed in over 90% of ovarian cancers. Olaparib is a PARP inhibitor that prevents the repair of DNA single-strand breaks. The combination of these two agents is intended to produce a synergistic effect: idetrexed induces DNA damage by inhibiting thymidylate synthesis, while olaparib prevents the repair of that damage, leading to synthetic lethality and cancer cell death. Dose Level 2 in the IDOL study represents the starting dose regimen, consisting of 9 mg/m² idetrexed administered intravenously and 300 mg olaparib administered orally.

Brand names

Lynparza

Other names

Dose Level 2 (IDOL Study)Idetrexed and Olaparib combination